Acute and chronic effects of morphine and naloxone on the phosphorylation of neurofilament-H proteins in the rat brain

Increased amounts of phosphorylated neurofilaments (pNF-H and pNF-M) are fo und in postmortem brains of opioid addicts. Because of the potential releva nce of aberrant pNF in opioid addiction (alterations of neuronal cytoskelet on and associated functions), the effects of opiate drugs on pNF-H were inv estigated in rat brain. Acute morphine (30 mg/kg, 2 h) induced a marked inc rease in the immunodensity of pNF-H in the cerebral cortex (93%). Chronic m orphine (10-100 mg/kg for 5 days) followed by opiate withdrawal resulted in a time-dependent decline in pNF-H (induction of tolerance). Thus, 2 h afte r the last dose of morphine, the abundance of pNF-H was still increased (27 %), which was followed (6-24 h) by down-regulation of pNF-H (5% increase at 6 h; 5% decrease at 12 h, and 29% decrease at 24 h). The acute (10 mg/kg f or 2 h) and chronic (2 x 10 mg/kg for 14 days) treatments with naloxone, an opioid receptor antagonist, did not alter pNF-H in the cerebral cortex, su ggesting that the opioid receptors (probably the ct-type) modulating the ph osphorylation state of NF-H are not tonically activated by endogenous opioi ds. The results indicate that morphine addiction is associated with an aber rant hyperphophorylation of NF-H in the rat brain. (C) 2001 Published by El sevier Science Ireland Ltd.